Extracts from the thymus gland are known as regulators of immune processes. For example, U.S. Pat. No. 5,070,026 to Morozov et al. (corresponding to Swiss patent No. CH 659,586) teaches a thymus gland preparation containing polypeptides of varying composition and their use in stimulating immunological activity and enhancing reparative processes and hemopoiesis. Goldstein et al. (Proc. Natl. Acad. Sci. U.S.A., 74(2):725-729, February 1997) teaches the isolation of thymosin, which comprises various biologically reactive polypeptides isolated from the thymus gland, and its use in enhancing immunological responses. U.S. Pat. No. 4,910,296 to Birr et al. and European Patent application Ser. No. 89/102569 to Lattanzi teach a composition containing human Thymosin Alpha 1 and fragments thereof which have immunoregulatory and immunostimulatory properties.
Thymic extracts consist of complexes of polypeptides. Their production from natural sources is limited by the complexity of the process, the relatively small yields of active substances, and the large variability of the physical, chemical characteristics and biological properties of the products. In addition, unwanted components which are present in natural thymic preparations sometimes cause side effects.
These problems create a demand for the identification and preparation of synthetic peptides. Several peptides with immunoregulatory properties have been synthesized (see, for example, SU 1,582,393; EP 230,052; U.S. Pat. No. 4,190,646; U.S. Pat. No. 5,008,246; and U.S. Pat. No. 5,013,723). Many scientific laboratories have tried to develop methods for preparing synthetic derivatives of natural peptides, which are more active than their natural analogs (see, for example, EP 0,136,720, 1984; EP 0,137,904, 1984).
Australian Patent No. AU-B-29308/89 (corresponding to WO 08906134) teaches the preparation of Glu-Trp and its use for treating immune deficiency conditions. WO 9308815 to Khavinson et al. discloses the peptide Glu-Trp and cyclic monomers and polymers thereof, for use in the treatment of immunosuppression. Semina et al. (Radiatsionnaya Biologiya Radioekologiya 33(3), 1993; WO 8906134) have shown that the levorotary (L) enantiomer of the dipeptide H-Glu-Trp-OH acts as an immunostimulant and can induce the proliferation of cells.
However, the known synthetic peptides do not always have the necessary immunoregulatory properties, and effectiveness. Furthermore, many of them are effective only in large doses that can cause side effects.